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American journal of human genetics DOI:10.1016/j.ajhg.2012.10.016

Disruption of a large intergenic noncoding RNA in subjects with neurodevelopmental disabilities.

Publication TypeJournal Article
Year of Publication2012
AuthorsTalkowski, ME, Maussion, G, Crapper, L, Rosenfeld, JA, Blumenthal, I, Hanscom, C, Chiang, C, Lindgren, A, Pereira, S, Ruderfer, D, Diallo, AB, Lopez, JP, Turecki, G, Chen, ES, Gigek, C, Harris, DJ, Lip, V, An, Y, Biagioli, M, Macdonald, ME, Lin, M, Haggarty, SJ, Sklar, P, Purcell, S, Kellis, M, Schwartz, S, Shaffer, LG, Natowicz, MR, Shen, Y, Morton, CC, Gusella, JF, Ernst, C
JournalAmerican journal of human genetics
Date Published2012/12/07

Large intergenic noncoding (linc) RNAs represent a newly described class of ribonucleic acid whose importance in human disease remains undefined. We identified a severely developmentally delayed 16-year-old female with karyotype 46,XX,t(2;11)(p25.1;p15.1)dn in the absence of clinically significant copy number variants (CNVs). DNA capture followed by next-generation sequencing of the translocation breakpoints revealed disruption of a single noncoding gene on chromosome 2, LINC00299, whose RNA product is expressed in all tissues measured, but most abundantly in brain. Among a series of additional, unrelated subjects referred for clinical diagnostic testing who showed CNV affecting this locus, we identified four with exon-crossing deletions in association with neurodevelopmental abnormalities. No disruption of the LINC00299 coding sequence was seen in almost 14,000 control subjects. Together, these subjects with disruption of LINC00299 implicate this particular noncoding RNA in brain development and raise the possibility that, as a class, abnormalities of lincRNAs may play a significant role in human developmental disorders.